Use of FDP and F1P Aldolase to Detect Tumorous and Nontumorous Tissue Damage by Ethanol Injection of Hepatocellular Carcinoma

Changes in serum levels of tumor-specificfructose 1,6-diphosphate (FDP) aldolase andnontumor-specific fructose 1-phosphate (F1P) aldolaseactivities were analyzed in patients with hepatocellularcarcinoma (HCC) to detect the damage of tumorous andnontumorous hepatic cells after percutaneous ethanolinjection (PEI). Initial PEI was performed in 20patients containing 22 HCC nodules with a diameter of4 cm. Changes in serum hepatic enzyme activities weremeasured before and after repeated PEI. FDP and F1Paldolase levels were measured by substrate-specificenzymatic methods. Pre- and posttreatment-fetoprotein (AFP) levels were determined byradioimmunoassay. The consequent changes in the totalnontumorous liver volumes after PEI were also analyzedby follow-up CT scans. Serum levels of FDP aldolasereleased by ethanol injection were progressivelyincreased (P < 0.0001) until the third PEI andthereafter decreased. In contrast, serum levels of F1Paldolase were continuously elevated even after the third PEI (P < 0.0001). Serum levels oftransaminases were also elevated after repeated PEI (P< 0.0001). The FDP/F1P aldolase ratio decreasedsignificantly with increased volume (>20 ml) ofinjected ethanol (P = 0.01) caused by nontumorous liverdamage. The elevation of FDP aldolase was markedlyassociated with a decrease in serum levels of AFP (P< 0.001), indicating adequate tumor necrosis. The progression of the total nontumor liver atrophydepended on the volume of injected ethanol andcorrelated significantly with F1P aldolase levels afterPEI (P < 0.01) but not with FDP aldolase. These results demonstrated that caution is needed toavoid nontumorous liver damage caused by the largevolume of ethanol injection in treating HCC. Measurementof FDP and F1P aldolase activities in serum after PEI is clinically useful to detect the degreeof tumorous and nontumorous tissue damage byethanol.     

针刺对视神经萎缩患者球结膜微循环的影响

本文对１８例２８眼视神经萎缩的针刺前后球结膜微循环变化进行了观察，并与正常组对照。结果发现视神经萎缩患者球结膜微循环以血流减慢、血细胞聚集、微血管了血和渗出为主要病理改变，针刺后血流加快、血细胞聚集减轻。本病球结膜微循环的异常发迹与中 对本病“经络郁滞”的认识相吻和。针灸能改善局部血循环，疏通目络气血、局部新陈代谢，使部分处于低下地视神经的兴奋性得以改善，是针炙治疗神经萎缩的疗效机制定之一。     

Helicobacter pylori and Mucosal Atrophy in Patients with Gastric Cancer (A Special Study Regarding the Methods for Detecting Helicobacter pylori)

We assessed the sensitivities of several methodsfor detecting Helicobacter pylori (culture, histology,rapid urease test, and serology), and evaluated the H.pylori positivity considering the degree of atrophy in the background mucosa in 202 gastriccancer patients and 101 controls. The positivity of H.pylori determined by culture (81%) was significantlyhigher than that determined by serology (62%) in gastric cancer patients (P < 0.001). Thepositivities of H. pylori determined by biopsy and/orserology in intestinal (84%) and diffuse (95%) types ofgastric cancer were higher than that observed in controls (54%) (P < 0.001).Intestinal-type gastric cancer tended to occur in theatrophic mucosa, in which H. pylori positivity was notdifferent from that in controls after adjusting for thedegree of atrophy, whereas diffuse-type gastric cancerwas observed more often in the nonatrophic mucosa, inwhich H. pylori positivity was higher than that incontrols even after adjusting for the degree ofatrophy.     

Clinical Application of Gastric Histology to Monitor Treatment of Dual Therapy in H. pylori Eradication

This preliminary study attempted to test whetherpretreatment gastric histology of H. pylori infectionmay affect the success of dual therapy and to identifywhich parameter of gastric histology could be improved after dual therapy. One hundredforty-five dyspeptic patients with H. pylori infectionreceived a two-week course of dual therapy (Amoxicillin500 mg every 6 hr plus omeprazole 20 mg twice a day). In each patient, three pairs of gastricbiopsies, sampled from the antrum, lower body, and upperbody near the cardia, were collected before treatmentand four weeks after completion of dual therapy. The density of H. pylori (score 1-5) and parametersof the modified Sydney system were applied to test theseverity of H. pylori-related gastric histology in eachspecimen. The total bacterial load (score 1-15) was a sum of the density of H. pylorisampled from three biopsies. The overall rate of H.pylori eradication rate by dual therapy is 73.1%(106/145). Univariate analysis of parameters inpretreatment histology disclosed that the presence ofmucosal atrophy (P < 0.01), lymphoid follicles (P< 0.005), and higher-density H. pylori (P < 0.001)predisposed to dual therapy failure. Multivariateanalysis by stepwise logistic regression further confirmed that boththe density of bacteria and the presence of lymphoidfollicles are the two major factors related to theoutcome of dual therapy (P < 0.001). Four weeks after dual therapy was completed, only patients withsuccessful eradication significantly improved in thesegastric histology parameters: acute activity, chronicinflammation, eosinophil infiltration, and mucosal atrophy. However, the lymphoid follicle andintestinal metaplasia were not significantly improvedduring the study period. The eradication rates amongthree subgroups with different total bacterial loads (group I: 1-5; II: 6-10; III: 11-15) discloseda downward trend (I: 89.1%; II: 73%; III: 52.7%). It isconcluded that dual therapy could improve gastrichistology especially among patients with successful eradication of H. pylori. Evaluatingpretreatment histologic parameters, including thedensity of H. pylori and the presence of lymphoidfollicles, is valuable in predicting the success of dualtherapy.     

Hindlimb Immobilization,But Not Castration,Induces Reduction of Undercarboxylated Osteocalcin Associated With Muscle Atrophy in Rats

Undercarboxylated osteocalcin (ucOC) has been implicated in skeletal muscle insulin sensitivity and function. However, whether muscle mass and strength loss in atrophic conditions is related to a reduction in ucOC is not clear. We hypothesized that both immobilization and testosterone depletion would lead to reductions in ucOC, associated with not only the degree of muscle atrophy but also changes to atrophy signaling pathway(s) in male rats. We subjected 8‐week‐old male Fischer (F344) rats to 7 days of hindlimb immobilization 10 days after castration surgery. Hindlimb immobilization, but not castration, resulted in a significant reduction in ucOC (30%) and lower ucOC was correlated with the degree of muscle loss and muscle weakness. ucOC levels, the expression of ucOC‐sensitive receptor G protein‐coupled receptor, class C, group 6, member A (GPRC6A), as well as the activity of extracellular signal‐regulated kinase (ERK) and 5′ adenosine monophosphate–activated protein kinase (AMPK) were associated with the expression and activity of a number of proteins in the mammalian target of rapamycin complex 1 (mTORC1) and Forkhead Box O (FOXO) signaling pathways in a muscle type–specific manner. These data suggest that ucOC may have other effects on skeletal muscle in addition to its insulin sensitizing effect. © 2016 American Society for Bone and Mineral Research.     

Metabolic activity of the subthalamic nucleus in a primate model of L-Dopa-unresponsive parkinsonism

Abstract

Increased activity of the subthalamic nucleus (STN) is critical in mediating motor symptoms of Parkinson's disease. To determine if altered STN activity also occurs in levodopa (L-Dopa)-unresponsive parkinsonism due to a combined nigral and striatal degeneration, metabolic activity of the STN was assessed using cytochrome oxidase (CO) histochemistry in monkeys with nigral, striatal, or nigral+striatal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and/or 3-nitropropionic acid (3NP). MPTP- and MPTP+3NP-treated monkeys had a similar parkinsonian score and were clinically indistinguishable. However, CO activity in the STN was significantly increased in MPTP-induced parkinsonism but not in MPTP+3NP-induced striatonigral degeneration. These results indicate that metabolic activity of the STN is normal following a combined nigral+striatal degeneration and may help to understand the lack of effect of STN stimulation in L-Dopa-unresponsive parkinsonism.     

中医治疗视神经萎缩临床观察

本文报道视神经萎缩44例计71眼,其病因以视神经炎及外伤所致者为多,分别为47.7％及22.7％。采用中药治疗,其中有光感以上视功能者57眼,经治疗后有视功能改善者32眼,14只无光感眼者治疗无效,总有效率为45％。黄斑中心凹光反射存在者45眼,有效26眼(57.8％),黄斑中心凹光反射消失者26眼,有效6眼(23.1％),统计学分析,两组比较差别有显著性(P<0.05)。结果提示视力损害与黄斑中心凹光反射及疗效相关,故黄斑中心凹光反射存在与否对中医治疗视神经萎缩预后判断具有一定的临床意义。     

Interdependence of Muscle Atrophy and Bone Loss Induced by Mechanical Unloading

Mechanical unloading induces muscle atrophy and bone loss; however, the time course and interdependence of these effects is not well defined. We subjected 4‐month‐old C57BL/6J mice to hindlimb suspension (HLS) for 3 weeks, euthanizing 12 to 16 mice on day (D) 0, 7, 14, and 21. Lean mass was 7% to 9% lower for HLS versus control from D7–21. Absolute mass of the gastrocnemius (gastroc) decreased 8% by D7, and was maximally decreased 16% by D14 of HLS. mRNA levels of Atrogin‐1 in the gastroc and quadriceps (quad) were increased 99% and 122%, respectively, at D7 of HLS. Similar increases in MuRF1 mRNA levels occurred at D7. Both atrogenes returned to baseline by D14. Protein synthesis in gastroc and quad was reduced 30% from D7–14 of HLS, returning to baseline by D21. HLS decreased phosphorylation of SK61, a substrate of mammalian target of rapamycin (mTOR), on D7–21, whereas 4E‐BP1 was not lower until D21. Cortical thickness of the femur and tibia did not decrease until D14 of HLS. Cortical bone of controls did not change over time. HLS mice had lower distal femur bone volume fraction (?22%) by D14; however, the effects of HLS were eliminated by D21 because of the decline of trabecular bone mass of controls. Femur strength was decreased approximately 13% by D14 of HLS, with no change in tibia mechanical properties at any time point. This investigation reveals that muscle atrophy precedes bone loss during unloading and may contribute to subsequent skeletal deficits. Countermeasures that preserve muscle may reduce bone loss induced by mechanical unloading or prolonged disuse. Trabecular bone loss with age, similar to that which occurs in mature astronauts, is superimposed on unloading. Preservation of muscle mass, cortical structure, and bone strength during the experiment suggests muscle may have a greater effect on cortical than trabecular bone. © 2014 American Society for Bone and Mineral Research.     

Vitamin D/Vitamin D Receptor Signaling Attenuates Skeletal Muscle Atrophy by Suppressing Renin-Angiotensin System

The nutritional level of vitamin D may affect musculoskeletal health. We have reported that vitamin D is a pivotal protector against tissue injuries by suppressing local renin-angiotensin system (RAS). This study aimed to explore the role of the vitamin D receptor (VDR) in the protection against muscle atrophy and the underlying mechanism. A cross-sectional study on participants (n = 1034) in Shanghai (China) was performed to analyze the association between vitamin D level and the risk of low muscle strength as well as to detect the circulating level of angiotensin II (Ang II). In animal studies, dexamethasone (Dex) was applied to induce muscle atrophy in wild-type (WT) and VDR-null mice, and the mice with the induction of muscle atrophy were treated with calcitriol for 10 days. The skeletal muscle cell line C2C12 and the muscle satellite cells were applied in in vitro studies. The increased risk of low muscle strength was correlated to a lower level of vitamin D (adjusted odds ratio [OR] 0.58) accompanied by an elevation in serum Ang II level. Ang II impaired the myogenic differentiation of C2C12 myoblasts as illustrated by the decrease in the area of myotubes and the downregulation of myogenic factors (myosin heavy chain [MHC] and myogenic differentiation factor D [MyoD]). The phenotype of muscle atrophy induced by Dex and Ang II was aggravated by VDR ablation in mice and in muscle satellite cells, respectively, and mediated by RAS and its downstream phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FOXO1) signaling. Calcitriol treatment exhibited beneficial effects on muscle function as demonstrated by the increased weight-loaded swimming time, grip strength, and fiber area, and improved fiber type composition via regulating ubiquitin ligases and their substrates MHC and MyoD through suppressing renin/Ang II axis. Taken together, VDR protects against skeletal muscle atrophy by suppressing RAS. Vitamin D could be a potential agent for the prevention and treatment of skeletal muscle atrophy. © 2021 American Society for Bone and Mineral Research (ASBMR).